Halting vaccine-derived poliovirus circulation: the novel type 2 oral vaccine might not be enough
Authors: Tolbert G Nyenswah, Jessica L Schue
Journal: The Lancet Global Health (2023)

Polio eradication remains elusive, and its progress has been hampered by the COVID-19 pandemic.1Burkholder B Wadood Z Kassem AM Ehrhardt D Zomahoun D The immediate impact of the COVID-19 pandemic on polio immunization and surveillance activities.Vaccine. 2023; 41: A2-11Crossref PubMed Scopus (0) Google Scholar Wild-type polioviruses are endemic in two countries (Afghanistan and Pakistan), but equally concerning is the ongoing spread of circulating vaccine-derived poliovirus type 2 (cVDPV2) several years after the switch to bivalent oral polio vaccine (bOPV).2Alleman MM Jorba J Greene SA et al.2020. Update on vaccine-derived poliovirus outbreaks — worldwide, July 2019–February 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 489-495Crossref PubMed Google Scholar The threat of a polio outbreak is greatest for countries with weak public health systems or affected by conflict. Since the transition from trivalent to bivalent OPV in 2016, community transmission of VDPV2 has continued despite the introduction of an inactivated polio vaccine. The WHO emergency use listing (EUL) of a novel OPV2 (nOPV2) was a promising and needed development in the fight against cVDPV2.3Macklin GR O'Reilly KM Grassly NC et al.Evolving epidemiology of poliovirus serotype 2 following withdrawal of the serotype 2 oral poliovirus vaccine.Science. 2020; 368: 401-405Crossref PubMed Scopus (60) Google Scholar However, in The Lancet Global Health, Stephen Kennedy and colleagues reported an unexpectedly low seroprevalence against type 2 poliovirus of 38·3% (95% CI 33·7–43·0) in Liberia after two nationwide campaigns with nOPV2.4Kennedy SB Macklin GR Mason Ross G et al.Poliovirus antibodies following two rounds of campaigns with a type 2 novel oral poliovirus vaccine in Liberia: a clustered, population-based seroprevalence survey.Lancet Glob Health. 2023; 11: e917-e923Summary Full Text Full Text PDF Google Scholar These findings suggest that this novel vaccine might not be the answer that is needed to fight against cVDPV2. Moreover, in March 2023, the Global Polio Eradication Initiative announced the detection of circulating cVDPV2 derived from nOPV2 in Burundi and DR Congo. Globally, the decline in childhood immunisation coverage has resulted in an increasing number of outbreaks of vaccine-derived polio, often emerging in countries that have remained polio-free for years.5Rachlin A Patel JC Burns CC et al.2022. Progress toward polio eradication— worldwide, January 2020–April 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 650-655Crossref PubMed Google Scholar Liberia eliminated polio in 2008. However, outbreak threats persist in the region and are exacerbated by low routine immunisation coverage. In 2019–20, just over half (51%) of children aged 12–23 months in Liberia received all basic vaccinations.6Liberia Institute of Statistics and Geo-Information ServicesLiberia Ministry of HealthThe DHS Program ICFLiberia demographic and health survey 2019–2020. Liberia Institute of Statistics and Geo-Information Services, Ministry of Health, and ICF, Monrovia, Liberia and Rockville, Maryland, USA2021Google Scholar With such low routine immunisation coverage, the country relies on supplementary immunisation activities (SIAs) to fill the gaps. With the risks associated with the original monovalent OPV2, there was much hope that the nOPV2 would be an effective replacement for the Sabin strain. The nOPV2 trial results demonstrated safety and showed a promise of efficacy through both clinical and immunological outcomes.7Global Polio Eradication InitiativeClinical summary for novel oral polio vaccine type 2. Global Polio Eradication Initiative, Geneva, Switzerland2022https://polioeradication.org/wp-content/uploads/2022/06/nOPV2-Clinical-Development-Summary_June-2022-Update_Final-EN.pdfDate accessed: February 26, 2023Google Scholar Under the EUL, nOPV2 has been used in several countries to respond to outbreaks, and data on the safety and genetic stability of the vaccine are promising.8Wahid R Mercer L Macadam A et al.2021. Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses.NPJ Vaccines. 2021; 6: 94Crossref PubMed Scopus (6) Google Scholar But what is less clear is the vaccine's efficacy. The immunological correlates of protection are well known for polio.9Plotkin SA 2010. Correlates of protection induced by vaccination.Clin Vaccine Immunol. 2010; 17: 1055-1065Crossref PubMed Scopus (1098) Google Scholar Therefore, serological surveys are a useful tool to measure population-level protection after an SIA and have proven their worth with other vaccine-preventable diseases.10Cutts FT Hanson M Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low- and middle-income countries.Trop Med Int Health. 2016; 21: 1086-1098Crossref PubMed Scopus (83) Google Scholar They can also be used to estimate vaccine coverage and validate or improve on administrative coverage estimates. The results presented by Kennedy and colleagues4Kennedy SB Macklin GR Mason Ross G et al.Poliovirus antibodies following two rounds of campaigns with a type 2 novel oral poliovirus vaccine in Liberia: a clustered, population-based seroprevalence survey.Lancet Glob Health. 2023; 11: e917-e923Summary Full Text Full Text PDF Google Scholar are concerning and stand in contrast to the immunogenicity results presented in the clinical trials.7Global Polio Eradication InitiativeClinical summary for novel oral polio vaccine type 2. Global Polio Eradication Initiative, Geneva, Switzerland2022https://polioeradication.org/wp-content/uploads/2022/06/nOPV2-Clinical-Development-Summary_June-2022-Update_Final-EN.pdfDate accessed: February 26, 2023Google Scholar Kennedy and colleagues point out two crucial concerns that might explain their findings, one biological and one social, both well known among vaccine scientists and professionals. First, is the difficulty in measuring vaccine coverage. Administrative coverage requires an estimate of the target population, which is often unknown, and coverage surveys rely on parental recall and/or proper vaccination documentation. These two estimates are rarely in agreement. Coverage surveys can have several sources of bias, and although checking a child's vaccination card is preferred, the cards are often only used for routine immunisations and don't include doses administered through SIAs. The wide range of coverage estimates the authors reported after the two SIAs highlights these issues. The second crucial point the authors discuss is the difference in vaccine response, particularly with vaccines administered orally, between high-income and low-income countries and among geographically diverse countries. This difference has been documented for several oral vaccines, including OPV.11Parker EP Ramani S Lopman BA et al.Causes of impaired oral vaccine efficacy in developing countries.Future Microbiol. 2018; 13: 97-118Crossref PubMed Scopus (103) Google Scholar With this evidence, the choice of countries—Belgium, Panama, and Bangladesh—for the phase 2 and 3 trials of this new vaccine is puzzling. This is a key equity issue with the way vaccines are developed. None of the countries where the phase 2 trials were conducted have ongoing outbreaks of wild-type or vaccine-derived polioviruses or are considered at risk of cVDPV2. The phase 3 trial results are still pending for Bangladesh (ClinicalTrials.gov NCT04579510), the only low-income country included. In conclusion, the reasons for the low seropositivity following the use of nOPV2 presented by Kennedy and colleagues should be thoroughly reviewed, and any future trials should be planned in countries that are at risk of cVDPV2 outbreaks. Regardless of the final decision on the use of the nOPV2, polio eradication efforts will rely on strengthening routine immunisation services and sustained acute flaccid paralysis surveillance. We declare no competing interests. Poliovirus antibodies following two rounds of campaigns with a type 2 novel oral poliovirus vaccine in Liberia: a clustered, population-based seroprevalence surveyUnexpectedly, the data showed low type 2 seroprevalence after two reported doses of nOPV2. This finding is probably affected by the lower oral poliovirus vaccine immunogenicity previously demonstrated in resource-limited settings, with high prevalence of chronic intestinal infections in children and other factors discussed herein. Our results provide the first assessment of nOPV2 performance in outbreak response in the African region. Full-Text PDF Open Access